Canine Pain Syndrome (CPS) is a spontaneous, acute necrotizing vasculitis of unknown etiology occurring primarily in young dogs. Approximately 40 to 50% of cases are subclinical and only documented on histopathological examination. The majority of cases have been reported in Beagle dogs used for biomedical research. CPS has a dramatic impact on the pharmaceutical industry and other laboratories that use dogs for biomedical and toxicological research since there is no screening test to identify susceptible dogs. It is considered that this syndrome may be a latent condition, the expression of which can be precipitated in predisposed dogs by drugs and other exogenous stimuli. The immunologic abnormalities and clinical features of CPS, including fever, leukocytosis, and elevated acute phase proteins, suggest an infectious etiology. The hypothesis to be tested is that CPS is an immunologically mediated generalized vasculitis that is triggered in susceptible dogs by an environmental agent, an infectious disease agent, or some combination of the two. The specific aims of this proposal are: 1. To further define the immunopathology of Canine Pain Syndrome 2. To determine if Canine Pain Syndrome has an infectious etiology. The proposed studies will be performed in Beagle dogs supplied by the nation's largest supplier of Beagle dogs for biomedical research. The long term goals are (1) to develop a preclinical screening test for dogs at risk of developing CPS (this is of prime importance for the biomedical research community), and, if possible, (2) to develop immunization and/or breeding programs to eliminate the disease.